Multilayer drug delivery system with barrier against reservoir material flow

• US 20060257462A1
• Filed: 05/12/2006
• Published: 11/16/2006
• Est. Priority Date: 05/13/2005
• Status: Active Grant

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Jansen, Rolf R., Coronado, Dina J.
• Granted Patent: US 8,632,800 B2
• Time in Patent Office: Days
• US Class Current: 424/448
• CPC Class Codes: A61F 13/0203 with fluid retention members
• CPC Class Codes: A61F 2013/0296 for making transdermal patches (chemical processes excluded)
• CPC Class Codes: A61J 3/00 Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: Y10T 156/1082 Partial cutting bonded sandwich [e.g., grooving or incising]

Abstract

A multilayered drug delivery system with a barrier suitable for delivery of drug through an individual'"'"'s body surface. By placing a barrier between two adjacent layers, unintended drug flow due to migration of a drug matrix between the adjacent matrix layers in the system to a patient is avoided.

Claims

1. A device for administration of a pharmaceutical agent to an individual through a body surface, comprising:

a. reservoir having a first matrix including at least one pharmaceutical agent in a first matrix, the reservoir having a reservoir outer perimeter;

b. first backing layer attached to the reservoir and substantially impermeable to the pharmaceutical agent;

c. layer of second matrix (second matrix layer) permeable to the pharmaceutical agent; and

d. barrier layer disposed between the reservoir and at least part of the second matrix layer, the barrier layer having a barrier layer outer perimeter, the reservoir outer perimeter being smaller than the barrier layer outer perimeter, the barrier layer being of a material that is substantially impermeable to the pharmaceutical agent.

2. The device of claim 1 wherein the barrier layer has a window through which at least one of a matrix and the first backing layer can extend to attach to the other.

3. The device of claim 1 wherein the barrier layer has a window through which at least one of a matrix and the first backing layer can extend to attach to the other and wherein the second matrix is an adhesive, wherein the reservoir and the first backing layer have flush edges and at least one of the first backing layer edges have material from the first matrix adhering thereto.

4. The device of claim 3 further comprising a second backing layer attached to the second matrix layer and is positioned more distal from the reservoir, the second backing layer having a second backing layer outer perimeter, the second matrix layer having a second matrix layer outer perimeter, the second matrix layer outer perimeter being larger than the barrier layer outer perimeter, and wherein the first backing layer has a first backing layer outer perimeter smaller than the second backing layer outer perimeter.

5. The device of claim 2 wherein the second matrix layer is a layer of adhesive that can adhere to the body surface maintaining the device thereon for 2 days or more and wherein the second matrix is the matrix that attaches to the first backing layer.

6. The device of claim 1 wherein the first matrix comprising an acrylate polymer in which the pharmaceutical agent is soluble.

7. The device of claim 1 further comprises a second backing layer attached to the second matrix layer and is positioned more distal to the reservoir and wherein the second matrix is an adhesive that can adhere to the body surface maintaining the device thereon for 2 days or more.

8. The device of claim 4 wherein the second matrix layer contains a second pharmaceutical agent.

9. The device of claim 1 wherein the device has an intended shelf life and the reservoir would cold flow during the shelf life such that the reservoir outer perimeter enlarges during the shelf life but does not exceed the barrier layer outer perimeter.

10. The device of claim 4 further comprising a third matrix attached to a third backing layer, the third backing layer having a third backing layer outer perimeter, the third matrix having a third matrix outer perimeter the same size as the third backing layer outer perimeter but larger than the outer perimeter of the barrier layer, the third matrix being disposed intermediate the reservoir and the second matrix layer and wherein the third matrix contains a second pharmaceutical agent.

11. The device of claim 4 further comprising a third matrix attached to a third backing layer, the third backing layer having a third backing layer outer perimeter, the third matrix having a third matrix outer perimeter the same size as the third backing layer outer perimeter but smaller than the window of the barrier layer, the third matrix being disposed intermediate the reservoir and the second matrix layer and extending in the window to attach to the first backing layer wherein the third matrix contains a second pharmaceutical agent.

12. The device of claim 4 wherein the device is made by mechanized mass production.

13. A device for administration of a pharmaceutical agent to an individual at a therapeutically effective rate through a body surface, comprising:

a. reservoir having a first matrix including at least one pharmaceutical agent in a first matrix, having a reservoir outer perimeter;

b. first backing layer attached to the reservoir and substantially impermeable to the pharmaceutical agent, having a first backing layer outer perimeter;

c. layer of adhesive second matrix (second matrix layer) permeable to the pharmaceutical agent, having a second matrix layer outer perimeter;

d. second backing layer attached to the second matrix layer, having a second backing layer outer perimeter; and

e. barrier layer disposed intermediate the reservoir and at least part of the second matrix layer, the barrier layer being of a material that is substantially impermeable to the pharmaceutical agent, the barrier layer having a window through which the second matrix layer and the first backing layer can adhere together at least in portion, the second backing layer outer perimeter being the same size as the second matrix layer outer perimeter and larger than the barrier layer outer perimeter, the first backing layer outer perimeter being the same size as the reservoir outer perimeter and smaller than the barrier layer outer perimeter.

14. A method of making a device for delivery of a pharmaceutical agent to an individual through a body surface, comprising:

a. cutting a reservoir layer and a first backing layer from a first web, the reservoir layer having a first matrix including at least one pharmaceutical agent in the first matrix, the first backing layer being substantially impermeable to the pharmaceutical agent, the reservoir layer being attached to the first backing layer and has a reservoir outer perimeter; and

b. adhesively affixing a barrier layer intermediate the reservoir layer and at least part of a second matrix layer on a second web, the second matrix layer being permeable to the pharmaceutical agent, the barrier layer being of a material that is substantially impermeable to the pharmaceutical agent, the barrier layer having a barrier outer perimeter, the reservoir outer perimeter being smaller than the barrier layer outer perimeter.

15. The method of claim 14 comprising cutting a window in the barrier layer, and affixing the barrier layer such that at least one of a matrix and the first backing layer can extend through the window to attach to the other, the first backing layer being disposed intermediate the second matrix layer and the reservoir.

16. The method of claim 15 further comprising cutting from a second web the second matrix layer attached to a second backing layer, the second backing layer having a second backing layer outer perimeter, the second matrix layer having a second matrix layer outer perimeter, such that the second matrix layer outer perimeter is larger than the barrier layer outer perimeter, and cutting the first web such that the first backing layer has a first backing layer outer perimeter that is smaller than the second backing layer outer perimeter.

17. The method of claim 15 further comprising feeding into a die system a web of reservoir layer material and first backing layer material and feeding into the die system a web of the second matrix layer material with the second backing material at different speed, cutting the web of reservoir layer material into discrete reservoir layers, and attaching the discrete reservoir layers on the web of second matrix layer material such that the discrete reservoir layers are spaced apart on the web of second matrix layer material.

18. The method of claim 14 wherein the first web and second web are mechanically cut by a machine that cuts in cycles of motion in mass production and wherein the reservoir and the first backing layer have flush edges resulting in at least one of the first backing layer edges have material from the first matrix adhering thereto before deployment of the device on an individual.

19. The method of claim 15 further comprising cutting from a third web a third matrix layer attached to a third backing layer such that the third backing layer has a third backing layer outer perimeter, and disposing the third matrix layer intermediate the reservoir layer and the second matrix layer, the third matrix layer having a third matrix outer perimeter the same size as the third backing layer outer perimeter but larger than the barrier layer outer perimeter and wherein the third matrix layer contains a second pharmaceutical agent.

20. The method of claim 19 further comprising machine-cutting another barrier layer having a window therein and adhesively affixing the another barrier layer intermediate the barrier layer and the reservoir layer, the another barrier layer having an outer perimeter smaller than the outer perimeter of the third matrix layer which in turn has a third matrix layer outer perimeter smaller than the outer perimeter of the barrier layer.

21. The method of claim 20 wherein the reservoir is for contacting the body surface, the method further comprising disposing layers in the device in an order of increasing distance from the body surface skin and in an order of increasing outer perimeter:

the reservoir layer, the another barrier layer, the third matrix layer, the barrier layer, and the second matrix layer.

22. The method of claim 15 further comprising cutting from a third web a third matrix layer attached to a third backing layer, such that the third backing layer has a third backing layer outer perimeter, disposing the third matrix intermediate the reservoir layer and the second matrix layer, the third matrix layer having a third matrix outer perimeter the same size as the third backing layer outer perimeter but smaller than the window;

affixing one of at least a portion of the third matrix layer and at least a portion of the first backing layer to the other through the window, wherein the third matrix contains a second pharmaceutical agent.

23. The method of claim 15 further comprising cutting to provide a frame shape to the barrier layer and attaching the framed shaped barrier layer to the second matrix layer on the second web.

24. The method of claim 15 further comprising sealing a protective pouch to enclose the layers.

25. The method of claim 14 wherein the second matrix layer contains a second pharmaceutical agent.

26. The method of claim 14 further comprising machine-cutting the barrier layer with the first backing layer from a web.

27. The method of claim 15 further comprising cutting from a third web a third matrix layer attached to a third backing layer and cutting another barrier layer having a window therein, the third matrix layer having an outer perimeter larger than the outer perimeter of the second matrix layer, the another barrier layer has an outer perimeter smaller than the outer perimeter of the third matrix but larger than the outer perimeter of the second matrix layer, disposing the third matrix layer on the side of the second matrix layer more distal from the reservoir, adhesively disposing the another barrier layer intermediate the third matrix layer and the second matrix layer, and wherein the second matrix layer contains a second pharmaceutical agent.

28. A method of making a device for delivery of a pharmaceutical agent to an individual through a body surface, comprising:

a. machine-cutting a reservoir layer and a first backing layer from a first web, the reservoir layer having a first matrix including at least one pharmaceutical agent in the first matrix, the first backing layer being substantially impermeable to the pharmaceutical agent, the reservoir layer being attached to the first backing layer and has a reservoir outer perimeter;

b. machine-cutting a second matrix layer from a second web having a second matrix material permeable to the pharmaceutical agent;

c. machine-cutting a barrier layer from a web having a barrier material that is substantially impermeable to the pharmaceutical agent, the barrier layer having a barrier layer outer perimeter and having a window smaller than the outer perimeter of the reservoir layer outer perimeter; and

d. adhesively affixing by machine the barrier layer intermediate the reservoir layer and at least part of the second matrix layer on a web including the second matrix layer, the reservoir outer perimeter being smaller than the barrier layer outer perimeter.

29. A method of making a device for delivery of a pharmaceutical agent to an individual through a body surface, comprising:

a. machine-cutting a reservoir layer and a first backing layer from a first web, the reservoir layer having a first matrix including at least one pharmaceutical agent in the first matrix, the first backing layer being substantially impermeable to the pharmaceutical agent, the reservoir layer being attached to the first backing layer and has a reservoir outer perimeter, such that the first backing layer has a first backing layer outer perimeter that is the same size as the reservoir layer outer perimeter;

b. machine-cutting a second matrix layer and a second backing layer from a second web, the second matrix layer being permeable to the pharmaceutical agent, the second backing layer having a second backing layer outer perimeter, the second matrix layer having a second matrix layer outer perimeter, such that the second backing layer outer perimeter is the same size as the second matrix layer outer perimeter;

c. machine-cutting a barrier layer from a web having a barrier material that is substantially impermeable to the pharmaceutical agent, the barrier layer having a barrier layer outer perimeter that is smaller than the second matrix layer outer perimeter and the barrier layer having a window smaller than the outer perimeter of the reservoir layer outer perimeter; and

d. adhesively affixing by machine the barrier layer intermediate the reservoir layer and at least part of the second matrix layer on a web including the second matrix layer, the reservoir outer perimeter being smaller than the barrier layer outer perimeter.